In the preliminary study, 24 patients who were within six weeks of diagnosis were randomly split into two groups. The 12 patients in the treatment group received the new drug, while the 12 patients in the control group did not. Nine of 12 patients in the treatment group experienced improved or equal insulin response over one year after just two weeks of treatment. Ten of the 12 control patients experienced the typical decline in insulin production. Furthermore, patients in the treatment group required significantly less insulin and had significantly lower HbA1c levels than patients in the control group. "After one year, the average insulin dose in the monoclonal-antibody group was below the level that is considered to indicate clinical remission (0.5 U per kilogram per day)," the researchers report.

Dr. Jeffrey Bluestone

Dr. Kevan Herold

How To Participate

Anyone interested in participating in future studies can contact Dr. Kevan Herold, the principal investigator, at the Naomi Berrie Diabetes Center at Columbia-Presbyterian in New York at (212) 305-5025.

Insights From the Researchers

We asked Dr. Kevan Herold, principal investigator, and Dr. Jeffrey Bluestone, one of the authors and inventor of the monoclonal antibody used in the study, for their comments on this exciting study.

From Dr. Herold

Of importance for patients with diabetes is that, unlike other immune
suppressive agents tried in diabetes, this agent appears to work for a long
period of time without the need for continuous administration, and
continuous immune suppression. This clearly reduces the potential
complications compared to the previously tried approaches.

We are also interested in determining whether the drug needs to be given
within the first 6 weeks after diagnosis or whether it may also be
effective beyond that point. We have proposed a trial for patients who have
had diabetes for 2 - 6 months. Of course, the obvious question that arises
is if islet cells are continuously produced in patients with diabetes but
eliminated by the immune response as soon as they develop, what would
happen if one was able to arrest the immune response. We don't have
information on this at this time but will be very interested in answering
it in the future.

From Dr. Bluestone

Question #1. What is the implication of this work for people developing Type 1 diabetes?

I believe that the major finding is that we can intervene early after disease onset to prevent further insulin-producing islet cell destruction. Beyond the fact that it seems to work well, the study has broad implications for supporting the use of other novel immunotherapies in new onset diabetes. It is my hope that we will eventually be able to cause permanent remission at this early stage of the disease

Question #2. Where do you go from here?

Obviously, although these results clearly show that we can slow down or even prevent progression of the disease in patients where we intervene early, a real cure will depend on either identifying these patients in the prediabetic state (before clinical disease) or replacing the insulin-producing cells through islet or stem cell transplantation. We are getting much better at predicting those patients at high risk and I hope that therapies such as the hOKT3g1 (Ala-Ala) will be tested in these individuals, to see if we can stop the disease before it causes clinical problems. As far as islet transplantation is concerned, we have already met with some success using this anti-CD3 monoclonal antibody in a small pilot study and are actively pursuing new clinical trials at both UCSF and University of Minnesota.

Question #3. Are there any potential uses of this drug beyond the setting of new onset diabetes

Given that the drug appears to selectively attack only disease-producing autoimmune cells, it is logical that this antibody would have many other applications in autoimmune diseases, as well as organ and bone marrow transplantation. We are currently testing the drug in psoriatic arthritis in an Immune Tolerance Network-sponsored phase II trial. It is also being tested for use in islet transplantation. In the future we hope to examine its usefulness in other disease settings.

Question #4. How does the drug work?

The anti-CD3 mAb acts on the T cells of the immune system - these include the cells responsible for the destruction of insulin production. The drug stimulates the production of protective immune signaling molecules to reorient the immune response from a destructive to a protective one. The antibody appears to selectively inhibit previously activated immune T cells involved in the disease process. So in effect, we're reprogramming the immune cells that, in diabetics, destroy the insulin-producing islet cells.

Question #5. Are there any concerns?

Anytime you treat someone with an immunosuppressive agent there are concerns about increased infections or other side effects. However, one of the strengths of this therapy is that right now, it is given over a short (2 week) period of time, limiting the long term side effects seen with other immunosuppressants. However, one of our major goals is to continue to develop therapies that are as specific as possible, targeting only the disease causing T cells while leaving the normal, disease-fighting part of the immune system to continue it's work.

Last Updated: Thursday February 27, 2014 19:28:21
This Internet site provides information of a general nature and is designed for educational purposes only. If you have any concerns about your own health or the health of your child, you should always consult with a physician or other health care professional.